An MS/MS analysis (which may also be referred to as a tandem analysis) is known as one of the mass spectrometric methods for identifying a substance with a large molecular weight and for analyzing its structure. A triple quadrupole (TQ) mass spectrometer is a typical MS/MS mass spectrometer. FIG. 6 is a schematic configuration diagram of a generally used triple quadrupole mass spectrometer disclosed in PATENT DOCUMENT 1 or other documents.
This mass spectrometer has an analysis chamber 11 evacuated by a vacuum pump (not shown). In this chamber 11, an ion source 12 for ionizing a sample to be analyzed, three quadrupoles 13, 15 and 17, each of which is composed of four rod electrodes, and a detector 18 for detecting ions and producing detection signals corresponding to the amount of detected ions, are arranged on an approximately straight line. A voltage composed of a DC voltage and a radio-frequency (RF) voltage is applied to the first-stage quadrupole (Q1) 13. Due to the effect of the quadrupole electric field generated by this composite voltage, only a target ion having a specific mass-to-charge ratio is selected as a precursor ion from various kinds of ions produced by the ion source 12. The mass-to-charge of the ion that is allowed to pass through the first-stage quadrupole 13 can be varied over a specific range by appropriately changing the DC voltage and the radio-frequency voltage applied to the first-stage quadrupole 13 while maintaining a specific relationship between them.
The second-stage quadrupole (Q2) 15 is contained in a highly airtight collision cell 14. A CID gas, such as argon (Ar) gas, is introduced into this collision cell 14. After being sent from the first-stage quadrupole 13 to the second-stage quadrupole 15, the precursor ion collides with the CID gas in the collision cell 14, to be dissociated into product ions by a CID process. This dissociation can occur in various forms. Normally, one kind of precursor ion produces plural kinds of product ions having different mass-to-charge ratios. These plural kinds of product ions are extracted from the collision cell 14 and introduced into the third-stage quadrupole (Q3) 17. In most cases, a pure radio-frequency voltage or a voltage generated by adding a DC bias voltage to the radio-frequency voltage is applied to the second-stage quadrupole 15 to make this quadrupole function as an ion guide for transporting ions to the subsequent stages while converging these ions.
Similar to the first-stage quadrupole 13, a voltage composed of a DC voltage and a radio-frequency voltage is applied to the third-stage quadrupole 17. Due to the effect of the quadrupole electric field generated by this voltage, only a product ion having a specific mass-to-charge ratio is selected in the third-stage quadrupole 17, and the selected ion reaches the detector 18. The mass-to-charge ratio of the ion that is allowed to pass through the third-stage quadrupole 17 can be varied over a specific range by appropriately changing the DC voltage and the radio-frequency voltage applied to the third-stage quadrupole 17 while maintaining a predetermined relationship between them. Based on the detection signals produced by the detector 18 during this operation, a data processor (not shown) creates a mass spectrum of the product ions resulting from the dissociation of the target ion.
As described in PATENT DOCUMENT 1, previously described mass spectrometer is capable of MS/MS analyses, such as a neutral loss scan measurement or precursor ion scan measurement. FIGS. 7A and 7B are model diagrams schematically showing how the mass-to-charge ratio of ions passing through the first-stage and third-stage quadrupoles 13 and 17 is changed in each of the aforementioned measurement modes: In the neutral loss scan measurement, as shown in FIG. 7A, a mass scan is performed while maintaining the mass difference (neutral loss) ΔM, i.e. the difference between the mass-to-charge ratio of the ions passing through the first-stage quadrupole 13 and that of the ions passing through the third-stage quadrupole 17. In the precursor ion scan measurement, as shown in FIG. 7B, the mass-to-charge ratio of the ions passing through the first-stage quadrupole 13 is changed while that of the ions passing through the third-stage quadrupole 17 is fixed at a certain value.
Another mode of the measurement that can be performed using a MS/MS mass spectrometer is a so-called auto MS/MS analysis, in which a specific kind of precursor ion that matches predetermined conditions is automatically detected and subjected to an MS/MS analysis. In this technique, a normal mode of mass analysis, which does not involve any dissociation process in the collision cell 14 or a mass-separation process by the third-stage quadrupole 17, is carried out to obtain a mass spectrum, immediately after which a data processing for automatically detecting a peak that matches predetermined conditions is performed on each of the peaks appearing on that mass spectrum. Then, an MS/MS analysis is performed for the detected peak, with the mass-to-charge ratio of that peak as the precursor ion, to create a mass spectrum of product ions.
The triple quadrupole mass spectrometer can perform the previously described various modes of MS/MS analyses including a dissociating operation. However, the following problem occurs since the dissociation of ions in the collision cell 14 occurs in the middle of their flight through a vacuum atmosphere:
The gas pressure inside the collision cell 14 is maintained at around several hundred mPa due to the almost continuous supply of the CID gas into the collision cell 14. This pressure is considerably higher than the gas pressure inside the analysis chamber 11 and outside the collision cell 14. When ions travel through a radio-frequency electric field under such a relatively high gas pressure, they gradually lose their kinetic energy due to collision with the gas, which decreases their flight speed. Therefore, a significant time delay occurs when the ions pass through the collision cell 14.
In the neutral loss scan measurement, the mass-scan operations of the first-stage and third-stage quadrupoles 13 and 17 are linked with each other. If a significant time delay of the ions occurs in the collision cell 14, which is located between the two quadrupoles, the mass-to-charge ratio of the ions actually analyzed in the third-stage quadrupole 17 will be different from the desired mass-to-charge ratio for the mass analysis. This causes the mass-to-charge ratio of the neutral loss to be shifted from the intended value, with a possible deterioration in the analysis sensitivity. In the auto MS/MS analysis, a similar deterioration in sensitivity of the analysis can occur due to a shift of the mass-to-charge ratio of the precursor ion selected by the first cycle of the mass analysis.
Furthermore, in any of the aforementioned measurement modes, the time delay of the ions in the collision cell 14 is not reflected in the mass spectrum. This means that the mass axis of the mass spectrum may be significantly shifted, causing a problem in the quantitative or qualitative analysis based on the mass spectrum.
To reduce the influence of the time delay of the ions in the collision cell 14, it is necessary to lower the scan speed in the mass-scan operation. However, this broadens the time interval of a repetitive measurement and thereby increases the possibility of missing a component in an LC/MS or GC/MS analysis. In recent years, the delay of the ions has been considerably reduced as a result of the development of high-speed collision cells, such as the products marketed as LINIAC™ or T-Wave™ (see Non-Patent Documents 1 and 2). However, even when such a high-speed collision cell is used, ions require several milliseconds to pass through the cell, so that the aforementioned sensitivity deterioration or mass shift will inevitably occur when the mass-scan speed is increased to a level around 1000 u/sec or higher.
Patent Document 1: JP-A 07-201304
Non-Patent Document 1: API 4000™ LC/MS/MS System, [online], Applied Biosystems Japan Kabushiki Kaisha, [searched on Feb. 2, 2009], Internet
Non-Patent Document 2: Tandem Quadrupole UPLC/MS Detector “ACQUITY™ TQD”, [online], Nihon Waters K.K., [searched on Feb. 2, 2009], Internet